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Headaches

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Headaches

  1. 1. Treatment of Headache Chris Boes MD Mayo Clinic Rochester, MN AAN Annual Meeting Therapy in Neurology Course March 18, 2013 Disclosures I have no relevant financial relationships to disclose at this time  Many medications used to treat migraine and other primary headache disorders do not have an FDA-approved indication for these purposes 
  2. 2. Goals/Objectives At the end of this talk you should be able to:  Outline effective treatments for migraine (including during pregnancy and lactation), chronic migraine, medication-overuse headache, tension-type headache, and cluster headache  Reasonably counsel migraine with aura patients about the risks of estrogencontaining OCs Note Will focus on treatments that are widely available at the current time  Will try to be practical and tell you exactly what I do (for better or worse) 
  3. 3. Outline Migraine  Tension-type headache  Cluster headache  Migraine without aura International Headache Society 2004 Diagnostic Criteria    At least five attacks fulfilling criteria below Headache lasting 4-72 hours (untreated or unsuccessfully treated) During headache has at least one of the following: – nausea and/or vomiting – photophobia and phonophobia   Headache has at least two of the following characteristics – unilateral – pulsating quality – moderate or severe intensity – aggravation by or causing avoidance of routine physical activity (walking or climbing stairs) Headache not attributed to another disorder
  4. 4. Goals of acute treatment  Immediate – Minimize pain – Treat associated symptoms – Minimize disability – Ultimate goal is freedom from pain within 2 hours, no headache recurrence or rescue meds within 24 hours, and no adverse events  Long-term – Avoid overuse – Minimize phone calls, urgent care, ED visits
  5. 5. Acute migraine treatment principles       Treat early Limit to 2 days per week (with exceptions) Use correct dose and formulation Use non-oral meds if: – early or severe nausea and vomiting, or – wakes up with migraine, or – severe migraine develops rapidly Assess patient’s side effect propensity Some patients respond to one drug and not another, try drug with 2 headaches before moving on Tip  Treat early at mild, but not too often – Some migraineurs have more than 10 headache days per month and are at risk for acute headache medication overuse – Those patients must ration their acute therapies to 10 days per month (or about 2 days per week) – One approach in this circumstance is to have the patient treat first with an NSAID, then if headache not better at 1 hour move to a triptan Taylor and Kaniecki, Curr Treat Options Neurol, 2011
  6. 6. Willis 1685  “the use of Millepedes ought not here to be omitted, or set lightly by, in regard that their express’d Juice, distill’d Water, and also the Powder prepar’d of them, often contribute egregiously to the Cure of ancient and obstinate Head-achs.” Aretaeus A.D. 81-?  For the treatment of headache, Aretaeus recommended inducing sneezing by placing testicle of beaver powder intranasally to “bring off phlegm”
  7. 7. Acute treatment options  Nonspecific – NSAIDs – simple analgesics – combination analgesics – antiemetics/neuroleptics – Isometheptene (recent removal of Midrin related to manufacturer’s compliance; Migragesic Ida and generic available now) – opioids  Specific – ergotamine/DHE – triptans AAN practice guideline: acute medications Use migraine-specific agents (triptans, DHE) in patients with moderate or severe migraine or whose mild-tomoderate headaches respond poorly to NSAIDs or combinations such as aspirin plus acetaminophen plus caffeine (Excedrin)  Specific treatments are preferred because of efficacy and lack of dependence, habituation, and addiction  www.aan.com/go/practice/guidelines; Silberstein, Neurology, 2000
  8. 8. Acute treatment: the evidence           Triptans (Class A) DHE-45 (Class A) Acetaminophen + aspirin + caffeine (Class A – studied in non-disabling attacks) Aspirin (Class A) Naproxen sodium (Class A) Ibuprofen (Class A) Butorphanol Intranasal (Class A) Sumatriptan/naproxen sodium (Class A) Diclofenac potassium (Class A) Prochlorperazine IV (Class A) Updated American Academy of Neurology Guidelines; in progress
  9. 9. Why treat early? Triptans block synaptic release of neuropeptides; this must occur before 2nd order neuron is sensitized TRIPTAN Sumatriptan Tabs 25,50,100 mg NS 5,20 mg SC 4,6 mg Dosepro SC 6 mg Suma + Naproxen Tabs 85mg +500mg Zolmitriptan Tabs 2.5,5 mg ZMT 2.5,5 mg NS 5 mg Naratriptan Tabs 1,2.5 mg Rizatriptan Tabs 5,10 mg MLT 5,10 mg Almotriptan Tabs 6.25,12.5 mg Frovatriptan Tab 2.5 mg Eletriptan 20, 40 mg Typical Dose May Repeat In Maximal Dose/day 100 mg 20 mg 6 mg 6 mg 2 hrs 2 hrs 1 hr 1 hr 200 mg 40 mg 12 mg 12 mg 1 tab 2 hrs 2 tabs 5 mg 5 mg 5mg 2 hrs 2 hrs 2 hrs 2.5 mg 4 hrs 10 mg 10 mg 2 hrs 2 hrs 30 mg 30 mg 12.5 mg 2 hrs 25 mg 2.5 mg 2 hrs 7.5 mg 40 mg 2 hrs 80 mg Tip: In general, give the highest 10 mg dose tablet available 10 mg 10 mg Exception: If patient is on propranolol, use rizatriptan 5 mg 5 mg not 10 mg
  10. 10. TRIPTAN Sumatriptan 50 mg Sumatriptan 25 mg Zolmitriptan 2.5 mg Zolmitriptan 5 mg Naratriptan 2.5 mg Rizatriptan 5 mg Rizatriptan 10 mg Eletriptan 20 mg Eletriptan 40 mg Eletriptan 80 mg Almotriptan 12.5 mg Initial 2 hour relief = = = = + =/+ +(+) = Sustained pain free = =/= = = + =/+ + + Consistency Tolerability =/= = = +(+) = = + = + = = ++ = = = = ++  = no difference when compared with sumatriptan 100mg  + better when compared with sumatriptan 100 mg  - inferior when compared with sumatriptan 100 mg  No Triptan is more safe than another as far as cardiac or Cephalalgia, 2002;22:633-658 vascular risks Formulary at my institution (accessed 1/28/13)     Tier 1G - Generic (preferred-lowest copay) – Ergotamine/caffeine PO – Isometheptene/Acetaminophen/Dichloralphenazone – Naratriptan PO – Sumatriptan PO – Rizatriptan PO (Note generic as of Jan 2013) Tier 1R - Generic, Restricted (preferred - lowest copay) – Sumatriptan NS Tier 2 - Brand (generic not available) – Ergotamine/caffeine PR Tier 2R - Brand, Restricted – Almotriptan PO – Dihydroergotamine NS – Eletriptan PO – Ergotamine SL
  11. 11. Formulary at my institution       Tier 2R - Injection, Restricted – Dihydroergotamine SC or IM (ampules and vials are generic) – Sumatriptan SC Tier 3 - Non-preferred or Lifestyle – Needle-free sumatriptan SC=Sumavel Dosepro Tier 3R - Non-preferred or Lifestyle, Restricted – Zolmitriptan NS Tier 4R - Non-formulary, Restricted – Frovatriptan PO – Zolmitriptan PO (both tab and rapid dissolve) Tier 4 - NF, Removed from Formulary – Ergotamine/Belladonna alkaloids/phenobarb PO Tier 5 - Excluded from the formulary, No Coverage – Sumatriptan succinate/naproxen sodium PO Dispensing limits at my institution Medication Dispensing limit Can refill every Sumatriptan, naratriptan, rizatriptan, eletriptan, almotriptan, zolmitriptan 54 tabs (all strengths) 100 days DHE nasal spray 6 kits (48 vials) 100 days DHE injection 20 vials 100 days Sumatriptan SC 6 kits (12 vials) 100 days Sumatriptan NS 36 sprays 100 days
  12. 12. Generic name Trade name Rizatriptan Zolmitriptan Frovatriptan Almotriptan Eletriptan Maxalt Zomig Frova Axert Relpax Anticipated patent expiration 12/1/2012 5/1/2013 12/2013 to 11/2015 11/1/2015 12/1/2016 These dates are projections and could change with patent and legal challenges Tip  Consider switching to nasal or injectable formulation after a patient has failed three oral triptans Goadsby and Sprenger, Lancet Neurol, 2010
  13. 13. Contraindications to triptans          Know or suspected ischemic heart disease Cerebrovascular disease Peripheral vascular disease Uncontrolled HTN Severe hepatic disease Use of ergot-alkaloid or other 5-HT1 agonist (i.e. a different triptan) within preceding 24 hours Patients should avoid sumatriptan, rizatriptan, and zolmitriptan within 2 weeks of MAO inhibitor use (phenelzine) Hemiplegic or basilar-type migraine Typically avoid during pregnancy Rational polytherapy Antiemetic (metoclopramide 10 mg) plus NSAID (Naproxen sodium 550 mg)  NSAID plus triptan  Antiemetic plus triptan  Antiemetic plus NSAID plus triptan 
  14. 14. Acute treatment: troubleshooting Recurrence • 2nd dose • Early Rx • Combination Rx Partial response • 2nd dose • Increase dose Inconsistency • Increase dose • Switch route or drug • Add prophylaxis Overuse • Establish use limits • Add prophylaxis No response • After 2 adequate trials, try another medication What not to use (or use with caution)  Barbiturate containing compounds – Implicated in overuse headache (rebound) and as a risk factor for headache progression – Lack evidence base, associated with dependence, habituation, sedation, and overuse headache (rebound) Exceptions • Established, infrequent, non-escalating use • Better alternatives contraindicated
  15. 15. What not to use (or use with caution)  Opioids – Implicated in overuse headache (rebound) and as a risk factor for headache progression – Associated with dependence, habituation, addiction and sedation Exceptions • Established, infrequent, non-escalating use • Better alternatives contraindicated • Rescue when 1st-line treatment fails Acute treatment plan  Initial Therapy First dose of triptan  Back-up Therapy Repeat dose of triptan  If Fails If Fails If has early or severe nausea and vomiting, or if wakes up with migraine, or if severe migraine develops rapidly use non-oral meds (stratified care) Rescue Therapy       Trying to keep out of ED Prochlorperazine 25 mg or chlorpromazine 100 mg PR Indomethacin 50 mg PR Ketorolac 31.5 mg IN Ketorolac 30-60 mg IM Very rarely opioid Whyte, Headache 2010; Turkewitz. Selfadministration of parenteral ketorolac for head pain. Headache, 1992
  16. 16. General counseling Encourage patient to sleep, eat, and exercise regularly  Limit caffeine to 2 normal sized beverages per day, or better yet avoid completely  Avoid alcohol if it is a trigger  Address risk factors for progression from episodic to chronic migraine Not Modifiable by Health Interventions Modifiable by Health Interventions Female gender Obesity Low socioeconomic status Medication overuse Head trauma Caffeine overuse Genetic/epigenetic? Stressful life events Snoring Depression Allodynia Modifications Can Result in:  Headache burden Migraine progression Rate of remission  Anxiety Attack frequency Scher  AI, et al. Headache 2008;48:16‐25. Bigal ME, Lipton RB. Curr Opin Neurol. 2009;22:269‐76.
  17. 17. CHRONIC DAILY HEADACHE Definition and Clinical Classification Headache ≥ 15 days per month Exclude secondary headache Diagnose Classify based on duration Short Duration < 4 hours Long Duration ≥ 4 hours “Wait a minute here, Mr. Crumbley. … Maybe it isn’t mechanical back pain after all.”
  18. 18. Chronic Daily Headache--Secondary Causes Chronic Daily Headache Secondary Causes
  19. 19. Primary CDH: Long Duration Chronic daily headache (≥ 15 d/M; ≥ 4 hours duration) Migraine ≥ 8 days/month YES Transformed or Chronic Migraine NO Continuous unilateral pain with autonomic features YES Hemicrania Continua NO Clear onset as a daily syndrome YES New Daily Persistent Headache NO Pain and associated symptom profile 2006 Revised Criteria for CM       YES Chronic Tension-Type Headache Headache (TT and/or migraine) on ≥15 days per M for at least 3 months Occurring in a patient who has had at least 5 attacks fulfilling migraine criteria On ≥8 days per month for at least 3 months headache has fulfilled 1 and/or 2 below: 1. Has at least two of: – Unilateral, pulsating, mod or severe, worse with routine activity And at least one of: • Nausea and/or vomiting • Photo and phono 2. Treated and relieved by triptan or ergot before the expected development of 1 above No medication overuse, not a secondary headache
  20. 20. 2006 Revised Criteria for MOH Headache present on ≥15 days/month  Regular overuse for >3 months of one or more acute treatment drugs  Ergotamine, triptans, opioids or combination analgesics on ≥10 days/M on a regular basis for >3 months  Simple analgesics or any combination of ergot, triptans, analgesics, opioids on ≥15 days/M on a regular basis for >3 months without overuse of a single class alone  Headache has developed or markedly worsened during med overuse  Medications Associated With MOH 60 Percentage (%) 50 48% 46% 40 33% 32% 30 18% 20 11% 10% Ergots NSAIDs 10 0 Butalbital compounds Acetaminophen Some using > 1 drug so total is > 100% Opioids Aspirin Triptans Bigal, Cephalalgia 2004;24:483-490
  21. 21. Stating the obvious Chronic migraine and medication overuse frequently coexist –45-80% of patients recruited into chronic migraine trials also meet criteria for MOH  Difficult to make accurate dx of MOH at time of presentation and even after treatment  Luckily, treatment approach is similar  Lipton’s simplified diagnosis of CM Lipton, Headache 2011;51(S2):77-83
  22. 22. Treatment overview        Provide patient education and address psychosocial issues Biobehavioral therapy (relaxation therapy, biofeedback) Withdraw overused acute medications +/- Initiate bridge therapy for withdrawal headache Initiate preventive medication Select acute therapy in the post-overuse setting; use ≤ 2 days per week Close f/u for 8-12 weeks Nonpharmacological measures       Eat, sleep, exercise in a regular pattern Limit caffeine Address comorbid depression and anxiety Training in relaxation techniques and biofeedback Educate that acute medication overuse may preclude the efficacy of preventives – Topiramate and onabotulinumtoxinA trials in chronic migraine cause some to ? this The headaches may get worse temporarily during withdrawal before subsequently improving
  23. 23. Fig 2.—Topiramate: impact of medication overuse on efficacy. aP < .02. bP = .03. Diener, Cephalalgia, 2007; Aurora, Headache 2011;51(S2):93-100 Similar results found in PREEMPT 1 and 2 trials of onabotulinumtoxinA: preventive was effective even if overusing acute headache medications Silberstein (PO49), Cephalalgia 2009;29(Suppl 1):31. Behavioral and physical treatments Behavioral Treatments Relaxation Level A Physical Treatments Cognitive Behavioral Biofeedback Level A Should be used Acupuncture Level A Level B Mobilization Cervical Manipulation Level U Level U Probably not Effective (? will be changed) Inadequate evidence Updated American Academy of Neurology Guidelines; in progress
  24. 24. Outpatient withdrawal protocol A  Taper overused acute medication over 4 weeks – Make the goal one of two things: • Aim to quit the overused acute medicine completely at end of wean, and use another acute med ≤ 2 d/week, or • Get the overused acute med down to ≤ 2 d/week  Sometimes use long-acting NSAID daily as bridge therapy over that time period  In butalbital overuse, if there is a concern for withdrawal symptoms, provide tapering course of phenobarbital 30 mg BID for 2 weeks, followed by 15 mg BID for 2 weeks In opioid overuse, if there is a concern for withdrawal symptoms, provide clonidine patch (0.1-0.2 mg/day/1 week) for 1-2 weeks   Start a preventive medication during the acute medication withdrawal After Tepper, Continuum Headache, August 2012 Outpatient withdrawal protocol B       I rarely use this approach This second outpatient approach is appropriate in the withdrawal of overused medications EXCEPT for barbiturates, opioids, or benzodiazepines Abrupt withdrawal of the overused medication Bridge therapy (long-acting NSAID, prednisone, or SC dihydroergotamine) At the end of the bridge, provide migraine-specific treatment, limited to ≤ 2 d/week Start a preventive medication on day 1 After Tepper, Continuum Headache, August 2012
  25. 25. Inpatient withdrawal protocol  Abrupt withdrawal of the overused acute medication – If abruptly withdrawing butalbital, start phenobarbital 30 mg BID for 2 weeks followed by 15 mg BID for 2 weeks – Opioids may need to be tapered rather than abruptly stopped if high doses are being overused – In opioid overuse, if there is a concern for withdrawal symptoms, provide clonidine patch (0.1-0.2 mg/day/1 week) for 1-2 weeks; alternatively clonidine can be given as needed for withdrawal symptoms (0.1-0.2 mg TID, titrated up or down based on symptoms)  IV bridge therapy (dihydroergotamine plus metoclopramide or ondansetron or domperidone, prochlorperazine, valproate sodium, or methylprednisolone)  Start a preventive medication See Nagy et al Neurology 2011 for inpatient IV DHE protocol Bridge therapies Naproxen  Prednisone  SC DHE  IV DHE plus metoclopramide  IV valproate sodium  IV prochlorperazine  IV methylprednisolone 
  26. 26. Guidelines for initiating migraine preventive therapy  > 3 headache days/M when acute treatment not reliably effective  > 8 days/M even if acute medications effective  Acute meds contraindicated, not tolerated, or ineffective  Patient preference  Uncommon migraine conditions (eg hemiplegic migraine) Preventive therapy        Goal is to decrease the headache frequency by 50% Start low, go slow until therapeutic effects develop, side effects develop, or ceiling dose is reached Preventive should be continued for approx 2 months at target dose or maximal tolerated dose before determining utility (some experts recommend 6 month trial) If the first is not helpful, taper it and try another from a different class Monotherapy preferred, but sometimes necessary to combine preventives Reliable birth control If the preventive is effective, it can be tapered after 6-12 months
  27. 27. Malayan tapir; Tapirus indicus Evidence-based episodic migraine prevention: Level A (established efficacy) Divalproex sodium  Sodium valproate  Topiramate  Metoprolol  Propranolol  Timolol  Petasites (butterbur)  Silberstein et al. Neurology 2012;78:1337-45; Silberstein et al. Neurology 2012;78:1346-53 I did not include preventives used to treat menstrually related migraine only
  28. 28. Evidence-based episodic migraine prevention: Level B (probably effective)          Amitriptyline Venlafaxine Atenolol Nadolol Magnesium MIG-99 (feverfew) Riboflavin Histamine SC NSAIDs: fenoprofen, ibuprofen, ketoprofen, naproxen, naproxen sodium Silberstein et al. Neurology 2012;78:1337-45; Silberstein et al. Neurology 2012;78:1346-53 I did not include preventives used to treat menstrually related migraine only Evidence-based episodic migraine prevention: Level C (possibly effective)           Lisinopril Candesartan Clonidine Guanfacine Carbamazepine Nebivolol Pindolol Cyproheptadine Co-Q10 NSAIDs: flurbiprofen, mefenamic acid Silberstein et al. Neurology 2012;78:1337-45; Silberstein et al. Neurology 2012;78:1346-53 I did not include preventives used to treat menstrually related migraine only
  29. 29. Evidence-based episodic migraine prevention: Level D (inadequate or conflicting data)          Acetazolamide Acenocoumarol Coumadin Picotamide Fluvoxamine Fluoxetine Gabapentin Protriptyline Bisoprolol         Nicardipine Nifedipine Nimodipine Verapamil Cyclandelate Omega-3 NSAIDS: aspirin, indomethacin Hyperbaric oxygen Silberstein et al. Neurology 2012;78:1337-45; Silberstein et al. Neurology 2012;78:1346-53 I did not include preventives used to treat menstrually related migraine only Dodick and Silberstein 2007   First choice – B-blockers – Flunarizine – Topiramate – Divalproex sodium or sodium valproate Second choice – Amitriptyline – Nortriptyline – Petasites/butterbur *2009 meta-analysis concluded that Botox is not sig better than placebo in EPISODIC migraine; Shuhendler et al, Pharmacotherapy, 2009  Third choice – Aspirin – Gabapentin – Magnesium – Candesartan – Lisinopril – OnabotulinumtoxinA* – Venlafaxine – Riboflavin – Coenzyme Q10 – Fluoxetine Dodick and Silberstein Practical Neurology 2007
  30. 30. 2010 Migraine Prevention Recommendations from Canada First-line agents  Amitriptyline  Propranolol  Nadolol Second-line agents  Topiramate  Gabapentin  Venlafaxine  Candesartan  Lisinopril  Magnesium  Butterbur  Coenzyme Q10  Riboflavin Third-line agents  Flunarizine  Pizotifen  Divalproex sodium Pringsheim, Davenport, and Becker. Prophylaxis of migraine headache. CMAJ 2010:182:269-276 2012 Migraine Prevention Recommendations from Canada Characteristic of the migraineur Drug strategy First timer Beta blocker, tricyclic Side effect averse Candesartan, Mg, riboflavin, butterbur, coenzyme Q10 Overweight Topiramate Hypertensive Beta blocker, candesartan, lisinopril Depressed/anxious Tricyclics, venlafaxine, dual therapy Canadian Journal of Neurological Sciences March 2012 supplement
  31. 31. Evidence base for preventive therapy in CHRONIC MIGRAINE Medication Amitriptyline Fluoxetine Nefazodone Divalproex sodium, valproate sodium Gabapentin Topiramate Tizanidine Dose 10-75 mg/day 20-40 mg/day Mean dose 300 mg/day 500-2500 mg/day 2400 mg/day 100 mg/day Mean dose 18 mg/day OnabotulinumtoxinA 155-195 U Evidence class III III III II II I III I (combined results of PREEMPT 1 and 2 lead to FDA approval in 2010) My typical regimens-ABCDE            Nortriptyline or amitriptyline: Start 10 or 25 mg qhs, then increase by 10 or 25 mg q week until on 1mg/kg qhs Propranolol: Use extended-release formulation and start 80 mg qd, increase in one week to 160 mg per day, some patients need up to 320 mg per day Nadolol: Start 40 mg qd, increase by 40 mg q week up to target of 120 mg/day, some patients need up to 240 mg/day Atenolol: 25 mg qhs X one week, then increase by 25 mg q week until on 50 mg BID Verapamil: Use sustained-release formulation starting at 120 mg/ day (1/2 of a 240 mg scored SR tablet) and increase in two weeks to 240 mg per day Depakote: Use Depakote ER starting at 500 mg per day and increase in 1 week to 1000 mg per day Gabapentin: Start 300 mg qhs, increase by 300 mg q week until on 2400 mg per day (600/900/900) Topiramate: Start 25 mg qhs, increase by 25 mg q week until on 50 mg po BID (some need 100 mg po BID) Tizanidine: Start 2 mg qhs, increase by 2 mg q week as tolerated up to 8 mg TID (most patients only tolerate 2 mg TID) Candesartan 16 mg per day Lisinopril 10 mg per day for 1 week, then 20 mg per day
  32. 32. OnabotulinumtoxinA Occipitalis  For chronic migraine, every 3 months  I almost always do 2 cycles  150 Units total: 50 U anterior mm plus both temporalis; 25 U in SC total; 25 U in each trapezius; 25 U in occipitalis total  Small number get neck pain post After Garza, Cephalalgia 2010;30:500-503. Doc, I don’t want to be: Courtesy of Dr. William Young
  33. 33. Scheduled opioid therapy  One prospective study reported the outcome in 70 pts who remained on scheduled opioid therapy for at least 3 years  74% either failed to show significant improvement or were discontinued from the program for clinical reasons Saper Neurology 2004 Other interventions
  34. 34. GON Block for Primary Headaches Prolonged Effects from a Single Injection Headache Disorder Migraine (54) Cluster (19) NDPH (10) Hemicrania Continua (7) Other (11) Partial Response 17 Complete Response 9 3 10 6 4 5 1 5 2 Mean duration of complete response 20 days Mean duration partial response 45 days Mean latency to response: 2 days Complete response: pain-free Partial response: >30% decrease in severity or frequency Afridi et al. Pain 2006;122;126-129 Occipital nerve stimulation for CM  ONSTIM trial – Feasibility study – Responder rate was 39%  PRISM trial – Did not meet primary endpoint – Works better if not overusing acute meds  St. Jude trial – Did not meet primary endpoint – Only pts with successful trial received implant  Other stimulation studies: – Combined occipital/supraorbital – Transcutaneous supraorbital stimulation preventively in EM • Schoenen et al Neurology Epub ahead of print 2/6/13 ONSTIM Cephalalgia 2011; PRISM Cephalalgia 2009 (abstract); St. Jude Cephalalgia 2012
  35. 35. ONB Not Predictive of ONS Outcome ONS Responsive ONS Nonresponsive ONB responder (10) 6/10 4/10 ONB non-responder (3) 2/3 1/3 No ONB performed (2) 1/2 1/2 Schwedt et al. Cephalalgia 2007; 27:271–274 CCQ: Treatment of the Pregnant Migraineur Relaxation techniques and – For severe acute attacks: biofeedback, regular meals and sleep • Hydration  Acute: • Mag sulfate 1 gram IV*** – For headache: • Metoclopramide 10 mg IV# † • Acetaminophen, +/- codeine • Prochlorperazine 10 mg IV • Codeine† • IV narcotics† can • Ibuprofen, naproxen (use in supplement 2nd trimester only)* – For prolonged attacks: • Hydrocodone, other narcotics† • Corticosteroids** – For nausea: – Sumatriptan does not appear • Metoclopramide to increase risk of birth • Chlorpromazine defects, but I still avoid • Prochlorperazine  Preventive: • Promethazine – I hardly ever use • Ondansetron** – Propranolol when benefits outweigh risks † 2011 case-control study found association between early pregnancy – Magnesium 400-600 qd****  opioid tx and certain birth defects; Broussard AJOG 2011 Boes, Adv Clin Neurosci Rehab, 2001; Goadsby, BMJ, 2008; *Marcus, Exp Rev Neurother, 2008; **Loder, Sem Neurology, 2007; ***Robertson, Sem Neuro, 2010;****Evers et al, EJN, 2009, #Friedman, Emerg Med Clin NA, 2009
  36. 36. CCQ: Treatment of the lactating migraineur  Acute: – Acetaminophen – Moderate caffeine – Ibuprofen, naproxen – AAP considers sumatriptan compatible with breastfeeding • Can try to take med just after breast-feeding or pump/discard following a dose – InfantRisk Center at Texas Tech states eletriptan is safer than suma as less detected in milk* – Magnesium sulfate – Opioids (other than codeine) Loder, Sem Neurology, 2007; AAP Committee on Drugs, Pediatrics, 2001; *Lucas, Curr Pain Headache Rep, 2009
  37. 37. CCQ: Treatment of the lactating migraineur  Preventive: – I nearly always recommend waiting until done breastfeeding – Propranolol, verapamil felt by AAP to be usually compatible with breast feeding – Canadians recommend magnesium and beta blockers, or amitriptyline/nortriptyline if that doesn’t work* *Pringsheim et al Can J Neurol Sci 2012 CCQ: Preventive treatment of frequent, prolonged, or prominent aura         Verapamil Aspirin 81 mg (experience in polycythemia vera; picotamide has been studied open label) Magnesium oxide 400 mg BID (Personal communication, Rozen) Divalproex sodium Gabapentin Acetazolamide (500-1000 mg total) Lamotrigine (50 to 300 mg total; mean 150 mg/d) Memantine Newman and Levin, eds. Headache and Facial Pain. Oxford: Oxford University Press, 2009: 55-56.; D’Andrea et al. Treatment of aura: solving the puzzle. Neurol Sci 2006;27:S96-S99.; Lampl et al. Lamotrigine reduces migraine aura and migraine attacks in patients with migraine with aura. JNNP 2005;76:1730-1732.
  38. 38. CCQ: Can my migraine with aura patient stay on estrogen-containing OC? My approach:           Relatively small increased risk of ischemic stroke in MA (RR 2) RR with OC 7, RR with smoking 9 in migraine of any type – Some of this data collected when higher dose estrogen used RR in MA currently using OC and smoking 10 Stroke can have significant morbidity/mortality Discuss what WHO and ACOG recommend Need an effective form of birth control when on a migraine preventive Some patients hear this and want to stop estrogen-containing OC; then progestin-only OC** (or progestin implant, IUD, or injection), copper IUD, barrier method, or other Many decide to stay on estrogen-containing OC If estrogen-containing OC clearly triggers or worsens aura then I recommend changing to progestin-only contraception or other If patient is a smoker and can’t quit, I recommend changing to progestin-only contraception or other **likely higher failure rate than combined OC Outline Migraine  Tension-type headache  Cluster headache  RR data: Kurth et al Lancet Neurol 2012
  39. 39. Recommended acute treatment tension-type headache Drug Dose Level of recommendation Ibuprofen 200-800 mg A Ketoprofen 25 mg A Aspirin 500-1000 mg A Naproxen 375-550 mg A Diclofenac 12.5-100 mg A Acetaminophen 1000 mg A Caffeine comb. 65-200 mg B Bendtsen et al, EFNS guideline, European Journal of Neurology, 2010 Recommended preventive treatment TTH Drug Daily dose Level of recommendation 30-75 mg A Mirtazapine 30 mg B Venlafaxine 150 mg B Clomipramine 75-150 mg B Maprotiline 75 mg B Drug of first choice Amitriptyline Drugs of 2nd choice Drugs of 3rd choice Bendtsen et al, EFNS guideline, European Journal of Neurology, 2010
  40. 40. Non-drug treatment of TTH Treatment Level of recommendation Psycho-behavioral treatments EMG biofeedback A Cognitive-behavioral therapy C Relaxation training C Physical therapy C Acupuncture C Bendtsen et al, EFNS guideline, European Journal of Neurology, 2010 Outline Migraine  Tension-type headache  Cluster headache 
  41. 41. St. Edward, Nebraska Cluster headache International Headache Society 2004 Diagnostic Criteria     Cluster headache has 2 key forms: 1. Episodic: occurs in periods (bouts) lasting 7 days to 1 year separated by pain-free periods lasting 1 month or more 2. Chronic: attacks occur for more than 1 year without remission or with remissions lasting less than 1 month      At least 5 attacks of severe or very severe unilateral orbital, supraorbital, and/or temporal pain lasting 15-180 min untreated Frequency from one qod to 8 per day Associated with one of: – ipsi conjunctival injection and/or lacrimation – ipsi nasal congestion and/or rhinorrhea – ipsi eyelid edema – ipsi forehead and facial sweating – ipsi miosis and/or ptosis – sense of restlessness or agitation Not attributed to another disorder Note: During part (but less than half) of the time-course, attacks may be less severe and/or of shorter or longer duration Note: During part (but less than half) of the time-course, attacks may be less frequent
  42. 42. Systematic review of cluster headache tx endorsed by AAN in 2010  Acute  Preventive  Level A: – Sumatriptan 6 mg SC – Zolmitriptan 5, 10 mg NS – Oxygen 6-12 L/min Level B: – Sumatriptan 20 mg NS – Zolmitriptan 5, 10 mg po Level C: – Lidocaine IN – Octreotide 100 mcg SC  Level A: – Nada Level B: – ONB – Civamide 100 microliter IN (not commercially available) Level C: – Verapamil – Lithium – Melatonin     Francis, Becker, Pringsheim, Neurology 2010;75:463-473 EFNS cluster headache guidelines           Acute: 100% oxygen, 15 l/min (A) Sumatriptan 6 mg s.c. (A) Sumatriptan 20 mg nasal (A) Zolmitriptan 5 mg nasal (A/B) Zolmitriptan 10 mg nasal (A/B) Zolmitriptan 10 mg oral (B) Zolmitriptan 5 mg oral (B) Lidocaine intranasal (B) Octreotide (B)           Preventive: Verapamil (A) Steroids (A) Lithium carbonate (B) Methysergide (B) Topiramate (B) Ergotamine tartrate (B) Valproic acid (C) Melatonin (C) Baclofen (C) A denotes effective, B denotes probably effective, C denotes possibly effective May, EJN, 2006
  43. 43. Acute treatment of cluster headache      Oxygen 7-15L/min for 15-20 min via non-rebreathing face mask (give them prescription and send them to oxygen supply store,not pharmacy) Sumatriptan 6 mg SC, limit 2 inj/ 24 hours (can also use 4 mg SC, then limit is 3 inj/24 hours) Sumatriptan 20 mg IN (only if attacks last at least 45 min)--used much less than SC because doesn’t work as well Zomig 5 mg IN  DHE 1 mg SC or IV Lidocaine 4-6% nasal drops, 2 drops in each nostril – patient has to lie down after dosing for 2-5 minutes, with head extended out of bed, bent downwards 30-45 degrees and rotated 20-30 degrees towards side of headache – rarely adequate on own as acute therapy, and difficult for cluster headache sufferers to tolerate as they are restless Halker, Vargas, and Dodick, Sem Neurol, 2010 Transitional Prevention of Cluster Headache   Prednisone 60 mg qd X 3 days, then decrease by 10 mg q 3 days until off – typically used once starting maintenance prevention as maintenance prevention takes a while to work – usually limited to 2-3 cycles per year GON blockade    *Ergotamine 1 mg po TID or 2 mg supp qd X 1-3 weeks – avoid triptan use acutely *DHE 0.5-1 mg SC or IM q 8-12 hours for 1-3 weeks or *repetitive IV DHE X 3 days – avoid triptan use acutely *Naratriptan 2.5 mg BID X 7 days or *eletriptan 40 mg BID X 6 days or *frovatriptan 2.5 mg qd X 7-20 days – avoid other triptan or ergot *placebo-controlled evidence lacking
  44. 44. Occipital Nerve Block in Cluster Headache: RPCT 23 ECH and CCH patients Placebo (10) 2.5ml betamethasone + 0.5ml xylocaine 2% ONB (13) Vs 2ml saline + 0.5ml xylocaine 2% Short-term response 0% Long-term response 0% P=0.0001 Short-term response 85% P=0.0026 Long-term response 61% 21g Ashkenazi, Levin, Dodick. In Wolff’s Headache 8th Ed Short-term response: Attack free within 72 h and sustained for 1 week Long-term response: Attack free withn 72 h and sustained for 1 month Ambrosini et al. Pain 2005;118:92-96 ONB for cluster headache: RPCT #2     Randomized, DB, placebo-controlled trial of suboccipital steroid (cortivazol) injections for transitional treatment of cluster headache 3 injections within 72 hours of each other Cortivazol group showed significant reduction in number of daily attacks in the 72 h period 2-4 days after the 3rd injection Question remains as to whether 3 injections provide better efficacy than a one-off Leroux et al. Lancet Neurol 2011;10:891-897
  45. 45. Maintenance Prevention of Cluster Headache    Short duration bouts may not require this Effective dose continued for typical duration of bout plus 2 weeks pain-free, then slow taper Baseline ECG, then verapamil 80 mg TID, increase by 80 mg q 2 weeks with ECG before each dose increase looking for PRinterval prolongation, initial target 480 mg/day but some need up to 960 mg/day    Lithium 300 mg TID, check trough level in approximately 1-2 weeks, trying to achieve a level of 0.7 to 1.0, may need to increase to 300/300/450 or 450/300/450 *Topiramate 25 mg qhs, increase by 25 mg every 3-4 days up to max of 200 mg po BID Melatonin 10 mg qhs *placebo-controlled evidence lacking Other CH Preventive Options     Nimodipine 60-120 mg/day *Nifedipine 30-180 mg/day *Methysergide (outside U.S.) – usually in ECH – up to 12 mg/day – start 1 mg qhs, then increase by 1 mg q 3d (in a tid regimen) until on 5 mg qd; then increase by 1 mg q 5 d up to 12 mg/day total; need one month break every six months or testing for fibrotic complications q 6 months – used less because of belief that you need to avoid triptans and ergots Pizotifen (outside U.S.) 3 mg qd            IN capsaicin and civamide *OnabotulinumtoxinA *Naratriptan 2.5 mg BID – must avoid other triptans or DHE acutely *Valproic acid 500-2000 mg/day – placebo-controlled trial negative but methodological issues *Gabapentin 800-3600 mg mg/day *Baclofen 10 mg TID *Chlorpromazine 75-700 mg/day *Transdermal clonidine 0.2-0.3 mg/day *Tizanidine 12-24 mg/day Leuprolide 3.75 mg IM X 1 Candesartan 32 mg/day *placebo-controlled evidence lacking
  46. 46. CH Surgical Treatment  Consider in those with refractory CCH Occipital nerve stimulation – Open-label studies – Most headache docs would do this before hypothalamic stim – Trial stimulation before permanent implantation is debated • Some improve within a few days of implant, others take weeks to months – Most patients need to continue their cluster headache preventive meds Hypothalamic stimulation (~66 patients, 63% responded)  Other surgery   Franzini Neurosurg Focus 2010 ONB Not Predictive of ONS Outcome ONS Responsive ONS Nonresponsive ONB responder (10) 6/10 4/10 ONB non-responder (3) 2/3 1/3 No ONB performed (2) 1/2 1/2 Schwedt et al. Cephalalgia 2007; 27:271–274
  47. 47. Goals/Objectives At the end of this talk you should be able to:  Outline effective treatments for migraine (including during pregnancy and lactation), chronic migraine, medication-overuse headache, tension-type headache, and cluster headache  Reasonably counsel migraine with aura patients about the risks of estrogencontaining OCs

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